Michiyoshi Yajima

Clinical Manifestations of Takayasu Arteritis in India and Japan— New Classification of Angiographic Findings:

In this retrospective review 102 Indian and 80 Japanese patients with Takayasu arteritis were compared in regard to their clinical manifestations and angiographic findings. Regardless of nationality, most patients were initially affected in their teens or twenties. Japanese patients were female in a larger ratio compared with the ratio in India. Clinically, the two groups exhibited several different features. More Japanese patients were found to be pulseless (P<0.01) whereas many Indian patients were hypertensive (P<0.01). Inflammatory conditions in Japanese patients were more severe (P<0.01) and tended to be more prolonged than those in the Indians. More Japanese patients suffered from aortic regurgitation (P<0.01), but Indians suffered from hypertension (P<0.01). Angiographic findings revealed that the aortic arch and its branches were mainly involved in Japanese patients (type I, IIa) whereas the abdominal aorta and its branches were mainly involved in Indian patients (type IV). However, the diffusely involved type (type V) was the one most commonly found in both countries. From the analyses of vascular lesions in both Indian and Japanese patients, 510 and 396, respectively, different progressions of vasculitis are speculated. In Japanese patients, vasculitis generally occurs in the ascending aorta, the aortic arch, and/or its branches and extends into the thoracic and abdominal aorta, subsequently forming various complicated lesions with prolonged inflammatory activity. On the other hand, in Indian patients, vasculitis generally occurs in the abdominal aorta involving renal arteries, subsequently extending into the thoracic aorta within one or two decades, simple vascular lesions being formed. Data analysis suggests that this morbid condition progresses differently in India and Japan, in spite of some common etiologic factor(s).

Thallium-201 stress scintigraphy in Takayasu arteritis

Thirty-eight women with Takayasu arteritis were studied using thallium-201 stress myocardial scintigraphy to assess the prevalence and pathophysiology of the perfusion abnormality. Twenty (53%) had abnormal scintigraphic findings (group A). Abnormal scans were divided into 3 groups: permanent defects in 6, reversible defects in 7 and slow washout in 7. The remaining 18 patients had normal scintigrams (group N). Group A had a tendency to be older and to have a high prevalence of complicated significant aortic regurgitation. Interventricular thickness plus left ventricular posterior wall thickness (26 +/- 7 vs 17 +/- 2 mm, p less than 0.01) and left ventricular mass (267 +/- 121 vs 133 +/- 39 g, p less than 0.01) were all greater in group A on echocardiography. The mean value of the central aortic pressure in systole was 170 +/- 15 mm Hg in the 7 catheterized patients in group A. Coronary ostial stenoses were present in 2 group A patients who showed reversible defects on scintigrams. These data indicate that the abnormal perfusion detected by imaging in patients with Takayasu arteritis was responsible for a decrease in coronary reserve or myocardial damage, or both, due to long-standing systemic hypertension or aortic regurgitation. Coronary artery disease should be considered if a reversible defect is present.

Comparative studies between Japanese and Korean patients: Comparison of the findings of angiography,HLA-Bw52, and clinical manifestations

SummaryA Japan-Korea cooperative survey on Takayasu arteritis has shown some differences in the features between Japanese and Korean patients with this disease. In angiographic findings, Japanese patients more frequently had lesions at the aortic arch and/or its branches (58% of 75 cases), while, in Korean patients, the abdominal aorta is the site of relatively frequent lesions (30% of 112 cases). Higher occurrence ofHLA-Bw52 was found in Japanese patients in comparison with Korean patients (46% vs 15%). The presence ofHLA-Bw52, however, might have a close association with Takayasu arteritis in Korea as well as in Japan. The complications in 126 Japanese and 88 Korean patients were also compared. The complications occurring with higher frequency in Japanese patients were aortic regurgitation, ischemic heart disease, and visual disturbances, while, in Korean patients, the more frequent complications were renovascular hypertension as well as hypertension of some other etiology.

Effects of thromboxane A2 injection on the rabbit coronary artery: II. The production of infarcts in cholesterol-fed animals

Abstract The role of thromboxane A 2 (TXA 2 ) in ischemic heart disease was studied using atherosclerotic rabbits fed a diet of pellets containing 1% cholesterol for 3 months, with agematched rabbits as controls. Various combinations of 15–30 μg of prostaglandin H 2 (PGH 2 ) and 1–5 mg of microsome protein obtained from cow platelets were injected at the origin of the aortic arch through an indwelling catheter. With this method, plasma levels of thromboxane B 2 of femoral arterial blood were over 1000 pg/ml immediately after injection of 30 μg of PGH 2 and 5 mg of microsome. The normal control groups showed no ECG changes related to myocardial damage. On the contrary, all of the cholesterol-fed rabbits exhibited a typical ST elevation in II, III, a Vf , and/or precordial leads at 3–5 min after injection of the TXA 2 -generating mixture, as well as a decrease in blood pressure and heart rate. All of these rabbits died within 40 hr except one given a mixture of minimum doses of PGH 2 (15 μg) and cow platelet microsome (1 mg protein). In two rabbits, the Q wave was observed. Various irregular-sized ischemic areas were frequently noted in the left ventricle and/or septal walls of the heart in these cholesterol-fed rabbits, using hematoxylin-basic fuchsin-picric acid stain and stains for detection of phosphorylase, LDH, and SDH activities. Microthrombi were frequently detected in the small coronary vessels, mainly at the subendocardial area of the myocardium. Such findings were not evident in the control group. These data suggest a role for thromboxane A 2 in the damaged myocardium and an association with coronary atherosclerosis.

Effects of thromboxane A2 injection on the rabbit coronary artery: I. Physiologic effects in healthy animals

Abstract Thromboxane A 2 (TXA 2 ), which is produced and released from platelets, has attracted much attention as a substance possibly related to myocardial infarction. In the present study, 10 μg of TXA 2 was injected into the coronary orifice area via a Swan-Ganz catheter which had been inserted through the carotid artery to the aortic root, to investigate the possibility of induction of myocardial infarction. Concomitantly, a comparison was made of the action of 10 μg/kg each of adrenaline (AD), angiotensin II (A II), collagen (CO), and arachidonic acid (AA). Administration of TXA 2 , CO, or AA induced no change in blood pressure and heart rate. Plasma TXB 2 was significantly elevated to reach 600–700 pg/ml, but no evidence of myocardial infarction was demonstrated. The administration of AD or A II brought about a significant elevation in blood pressure and arrhythmia accompanied by A-V block and ST depression, but these changes were all transient and myocardial infarction was not induced. These results indicate that at the dose used in the present experiment TXA 2 cannot induce thrombus formation in a nondiseased coronary artery. Further studies using a larger dose of TXA 2 in cholesterol-fed rabbits are under way.

Prostacyclin and Variant Angina

Plasma levels of thromboxane B2 (TXB2) and 6-keto PGF1 alpha in the blood samples taken at the coronary sinus and ascending aorta from twenty-one Japanese patients with variant angina and twenty with effort angina were measured by radioimmunoassay, the objective being to search for the contribution of prostanoids in coronary spasm. The data were compared with data on thirteen subjects free from coronary artery diseases. In coronary sinus blood, plasma TXB2 in patients with effort angina exhibited statistically significant high levels, as compared with data in the controls. These with variant angina also had high levels, albeit without a statistically significant difference. Eight patients with variant angina and for whom the coronary angiogram showed more than 50% of narrowing had statistically significant high levels of TXB2, and the other thirteen with variant angina and normal coronaries or less than 50% of narrowing had the same plasma levels of TXB2 as the controls. In contrast to TXB2, the plasma levels of 6-keto PGF1 alpha in both coronary sinus and aortic blood of patients with variant angina were very low, as compared with normal controls. Statistically significant low levels of 6-keto PGF1 alpha were noted in the coronary sinus blood of patients with variant angina with normal coronaries and in the aortic blood of those with variant angina, as compared with data on the normal controls. Neither ergonovine test nor spontaneous attacks in patients with variant angina revealed characteristic changes in levels of TXB2 and 6-keto PGF1 alpha in the coronary sinus. These data suggest that high levels of TXB2 in patients with atherosclerotic coronaries may be one factor leading to spasm, while low levels of PGI2 may be a contributing factor.

Antiplatelet Therapy for Atherosclerotic Disorders

Recent studies have revealed the important roles of platelets in atherogenesis via vascular injury. Our in vivo and in vitro studies clearly demonstrate that activated platelets directly inflict injury to vascular endothelial cells, which is associated with a decrease in intracellular cyclic AMP levels in vascular tissues. Antiplatelet therapy is clinically important not only for the prevention of thrombotic episodes but also for the prevention of vascular injury and atherosclerosis. A small dose of aspirin (80 mg) induces clinically hypoaggregativeness of platelets with concomitantly decreased levels of thromboxane A2 in plasma. Our clinical study involving more than 3 years of treatment with small doses of aspirin demonstrated favorable therapeutic effects characterized by hypoaggregation of platelets and increased levels of cAMP and 6-keto PGF1 alpha in plasma which will aid in the prevention of atherosclerosis.

Human leucocyte antigen in variant angina

Human leucocyte antigen analysis of 45 patients with variant angina was performed to determine the presence of causative genetic factor(s). A significantly low frequency of human leucocyte antigen DQ omega 3 was found in these patients, as compared with that in 152 normal Japanese adults. There were no differences in frequencies of antigens between patients with normal and those with atherosclerotic coronaries. These data suggest that some genetic factor(s) may contribute to the pathogenesis of coronary spasm.

Enhanced flow velocity increase through the left ventricular inflow tract of patients with isolated aortic regurgitation

Twenty-five patients with chronic aortic regurgitation (AR), and 12 control subjects were studied using Doppler echocardiography to investigate the effects of AR on transmitral flow. Peak early filling velocities at the levels of the mitral valve tips (E1) and annulus (E2) were measured, and the transmitral flow restriction index (delta E = (E1-E2)/E2) was obtained. Patients with AR were classified into 2 groups according to the ratio of the cross-sectional area of the regurgitant jet to that of the left ventricular outflow tract. Group I had the ratio less than 0.20, and group II had greater than or equal to 0.20. E2 in group II was lower than in control subjects, whereas E1 was not significantly different in any groups. delta E in group II was higher than in group I or in control subjects (p less than 0.05 and 0.01, respectively). delta E showed a significant correlation with the cross-sectional area ratio in all patients with AR (r = 0.70, p less than 0.01) and in group II (r = 0.82; p less than 0.01). Our data suggest that AR restricts early transmitral filling, and that delta E may indicate the increased driving pressure caused by flow restriction and is a useful hemodynamic index of AR.

Microassay of cyclic nucleotides in vessel wall: V. Simultaneous assay of cyclic AMP and cyclic GMP

Abstract Cyclic GMP (cGMP) is an important key substance in cell function; however, the related mechanisms have not been entirely elucidated, as the content of this nucleotide within the cell is so small that an accurate estimation is difficult. We designed a microassay for cyclic GMP in 500 μg dry weight of tissue samples, using succinylation, and were able to assay, separately, the content of cyclic GMP in the intima or media of the arterial wall. In addition, we attempted to develop a method for a simultaneous determination of both cyclic AMP and cyclic GMP in a small amount of the same assay mixture. Five hundred micrograms dry weight of intima or media of rabbit aorta was prepared under a stereomicroscope. After deproteinization and lyophilization, the samples were dissolved with 60 μl of H 2 O and 30 μl of succinylation mixture. After succinylation, 40 μl of each of the tissue extractions was sampled to determine the levels of cyclic AMP and cyclic GMP. The radioimmunoassay was performed, using Yamasas kit. The recovery rates of cyclic AMP and cyclic GMP in our method were 86.2 ± 1.2 and 87.6 ± 1.3%, respectively. The levels of cyclic GMP in the intima and media of aorta of cow, pig, and rabbits were estimated to be, intima: 0.18 ± 0.02, 0.06 ± 0.03, and 0.20 ± 0.01 pmole/mg protein, media: 0.08 ± 0.01, 0.04 ± 0.01, and 0.09 ± 0.01. The cyclic GMP levels in the intima of aorta of cow and rabbits were high compared to levels in the media and this difference was statistically significant ( P